This Phase 1/1b, open-label, first-in-human, monotherapy study will be conducted in 2 parts. Part A will consist of the SRF231 monotherapy dose-escalation portion of the study, and will enroll up to 48 patients with advanced solid tumors and hematological cancers. Part B will include monotherapy expansion cohorts in advanced solid and hematologic cancers to further examine SRF231 as monotherapy (100 patients total).
This first-in-human study is designed to evaluate the safety and tolerability of SRF231 as a monotherapy via dose escalation (Part A), and to determine the dose(s) of SRF231 to be further examined in expansion cohorts as monotherapy. The preliminary clinical activity of SRF231 administered as monotherapy will be characterized, along with pharmacokinetics (PK) and pharmacodynamics. In Part B, the safety and tolerability of SRF231 as monotherapy will be evaluated in select patient cohorts of advanced cancers and evaluate clinical activity. The study also is designed to examine the effect of SRF231 monotherapy on peripheral blood immune cell subsets, peripheral blood gene expression, and serum biomarkers
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
148
SRF231 specifically blocks the interaction between CD47 and signal regulatory protein alpha and acts as a potent enhancer of human tumor cell phagocytosis.
Research Site 002
New York, New York, United States
Research Site 001
San Antonio, Texas, United States
Research Site 101
Toronto, Ontario, Canada
[Part A] Dose-limiting toxicity (DLT)
The number of patients in Part A who experienced a DLT during Cycle 1 or completed at least 75% of the prescribed Cycle 1 SRF231 dose will be used to assess tolerability and determine the appropriate dose for Part B.
Time frame: Through 24 months with 21 day drug treatment cycles
[Part A] Non-tolerated Dose (NTD)
For Part A, the NTD is the dose level at which 2 or more patients experience a DLT in the first cycle of treatment.
Time frame: Through 24 months with 21 day drug treatment cycles
[Part A] Maximum tolerated Dose (MTD)
For Part A, the MTD is defined as the dose level immediately below the non-tolerated dose (NTD). A total of 6 patients must be treated at a dose level for it to be considered the MTD.
Time frame: Through 24 months with 21 day drug treatment cycles
[Parts A and B] Safety Analysis: summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs)
Safety and tolerability of SRF231 monotherapy will be assessed by summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that emerges or worsens in the period from the first dose of study treatment to 30 days after the last dose of study drug assessed by per CTCAE version 4.03 or higher.
Time frame: Through 24 months with 21 day drug treatment cycles
[Parts A and B] Maximum serum concentration (Cmax) of SRF231
Cmax in serum for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.
Time frame: Up to 24 months
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[Parts A and B] Time to maximum serum concentration (tmax) of SRF231
Tmax in serum for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.
Time frame: Up to 24 months
[Parts A and B] Area under the serum concentration-time curve from time zero to the last quantifiable time point (AUC 0-last) of SRF231
AUC 0-last for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods
Time frame: Up to 24 months
[Parts A and B] Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC 0-INF) of SRF231
AUC 0-INF for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.
Time frame: Up to 24 months
[Parts A and B] Terminal elimination half-life (t1/2) of SRF231
T1/2 for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.
Time frame: Up to 24 months
[Parts A and B] Pharmacodynamics of SRF231 via receptor occupancy
Blood samples will be collected from all patients at multiple time points for analysis of CD47 receptor occupancy by SRF231. PD analyses will be descriptive and summary tabulations may be produced.
Time frame: Up to 24 months
[Parts A and B] Anti-Drug Antibodies (ADAs). Time Frame: Up to 24 months
Determine the incidence of ADAs in all patients who receive at least one dose of SRF231 and had at least one measurable sample.
Time frame: Up to 24 months
[Part B] Overall Response Rate (ORR) including the best response of complete response (CR) or partial response (PR)
ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria.
Time frame: Up to 24 months
[Part B] Duration of Response (DOR) including time from the first documented to response to documented disease progression
DoR defined as the time from first documented response to documented disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria will be summarized.
Time frame: Up to 24 months
[Part B] Disease Control Rate (DCR) as the percentage of patients with CR, PR, or stable disease (SD)
DCR defined as the percentage of patients with CR, PR or SD determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria will be summarized.
Time frame: Up to 24 months
[Part B] Progression Free Survival as the time from first treatment to death or documented disease progression
PFS defined as the time from the first treatment on study to death or documented disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria will be summarized.
Time frame: Up to 24 months